1. Field of the Invention
The present invention relates to a particle agglutination pattern judgment method for optically measuring patterns of particles in sample solutions and automatically classifying attributes of patterns into agglutination, non-agglutination, and others.
2. Description of the Related Art
A conventional particle agglutination pattern judgment apparatus for judging agglutination, non-agglutination, and other patterns of particles in solutions is known, as disclosed in U.S. Pat. No. 4,727,033. The particle agglutination pattern judgment apparatus optically measures particle patterns, obtains parameters for attribute judgment, and compares the parameters with a predetermined threshold value to judge criteria to which attributes of the patterns belong.
In the particle agglutination pattern judgment apparatus, an unidentified pattern whose attribute cannot be automatically classified to agglutination/non-agglutination patterns tends to be found in the following cases:
(1) when particles themselves in a sample solution are abnormal (hemolysis of blood cells, abnormality of a particulate reagent, and the like);
(2) when a reagent which reacts with particles in a sample solution or a sample (e.g., an anti-A serum against a blood reagent, an anti-B serum reagent, a serum against a blood cell reagent, blood plasma, and the like) is abnormal, and a correct pattern cannot be formed;
(3) when a foreign matter is mixed in a sample solution;
(4) when a predetermined threshold value for executing automatic agglutination/non-agglutination judgment is not set to be a correct value for any reasons;
(5) when an operator at the particle agglutination pattern judgment apparatus gives priority to a visual judgment mode, and sets a threshold value which causes an automatic judgment result near a boundary of agglutination/non-agglutination patterns to indicate an unidentified pattern;
(6) when an original pattern cannot be formed due to, e.g., activation of a complement;
(7) when a microplate or the like is damaged; and
(8) when the apparatus or the like causes an error.
When an unidentified pattern is generated in the above cases, an operator at the particle agglutination pattern judgment apparatus reexamines a sample which is determined as the unidentified pattern by visual observation using a visual judgment unit of the particle agglutination pattern judgment apparatus or a technique therefor, and corrects output data from a printer of the particle agglutination pattern judgment apparatus based on the visual judgment result. However, when the operator corrects data based on the visual judgment result, the following problems are
(1) The operator must visually find a sample determined as an unidentified pattern by the particle agglutination pattern judgment apparatus, resulting in cumbersome operation.
(2) There is a time difference between when automatic judgment is performed in the particle agglutination pattern judgment apparatus and when the operator performs visual judgment, and the reason why the particle agglutination pattern judgment apparatus judges an unidentified pattern cannot be accurately recognized. More specifically, if there is a time difference, a pattern may be changed over time.
(3) Automatic judgment by the particle agglutination pattern judgment apparatus and visual judgment by the operator may often have different physical factors such as a vibration which changes a pattern. For this reason, the reason why the particle agglutination pattern judgment apparatus judges an unidentified pattern cannot often be accurately recognized.
(4) In any case, a judgment result correction operation requires cumbersome operations to search data of a sample which is determined as an unidentified pattern by the pattern judgment apparatus from printer output data, to visually rejudge a corresponding well of a microplate, and correct the result with a red pen.
These problems become serious especially in the large-scale particle agglutination pattern judgment apparatus having a high processing speed, thus causing artificial and other errors.
The predetermined threshold value must be properly set depending on differences in conditions to be described below, and must be changed depending on them:
(1) kinds of particles in a sample solution;
(2) a density of particles in a sample solution;
(3) kinds and a density of a reagent which reacts with particles or a sample; and
(4) judgment reference of an operator who operates the particle agglutination pattern judgment apparatus.
In general, an operator inputs a threshold value determined based on these conditions in advance in the particle agglutination pattern judgment apparatus using an input unit such as a keyboard.
However, a method of judging attributes of patterns using the particle agglutination pattern judgment apparatus adopting such a threshold value setting method has the following problems:
(1) A threshold value is obtained by numerically expressing a predetermined portion of an agglutination pattern. It is difficult to associate the numerical value with a particle pattern, and it is cumbersome to determine a threshold value.
(2) In particular, when a plurality of threshold values are set and are associated with each other, it is very difficult to determine a proper value.
(3) Even if a threshold value is input as described above, the input value must be corrected and adjusted by try & error judgment experiments, and much time is required for setting a threshold value.
(4) An input operation at a keyboard or the like is troublesome for an operator who is not accustomed to the keyboard, and this may cause an operation error.